title: The changing landscape in metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  The treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) has significantly changed in the recent years. We provide an updated summary of the new therapeutic agents in this disease and discuss open questions and future challenges.
  
  
  RESULTS
  mCRPC is now known to frequently retain sensitivity to hormonal manipulation even after the development of castration resistance, and both the androgen synthesis inhibitor abiraterone and the androgen-receptor antagonist enzalutamide have recently shown to prolong survival in mCRPC patients after chemotherapy. Cabazitaxel, a new-generation antitubulin chemotherapeutic, and the radionuclide radium-223 chloride have also been shown to prolong survival. The biological agent cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against Met and vascular endothelial growth factor receptor 2, demonstrated promising results in a phase II trial and is currently being assessed in two large randomized phase 3 controlled trials.
  
  
  CONCLUSIONS
  This recent progress is unprecedented and has already translated to a significant increase in the available armamentarium of drugs for mCRPC. Nonetheless, there are still significant unresolved questions as to the proper sequencing of these novel drugs along the disease continuum. Moreover, the problem of drug resistance, either primary of acquired, continues to be a major therapeutic obstacle.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use; D011788:Quality of Life; D011868:Radioisotopes / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D011725:Pyridines; D011868:Radioisotopes; D043823:Taxoids; C558660:cabozantinib; D010669:Phenylthiohydantoin; C552428:cabazitaxel; C540278:enzalutamide; D020794:Receptor Protein-Tyrosine Kinases; C581106:radium Ra 223 dichloride; D011883:Radium